CN115645150A - Medical dressing with repair matrix - Google Patents

Medical dressing with repair matrix Download PDF

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Publication number
CN115645150A
CN115645150A CN202211287212.3A CN202211287212A CN115645150A CN 115645150 A CN115645150 A CN 115645150A CN 202211287212 A CN202211287212 A CN 202211287212A CN 115645150 A CN115645150 A CN 115645150A
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layer
wound
medical dressing
examples
intermediate layer
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CN202211287212.3A
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Chinese (zh)
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陈丽
侯新国
闫鹏
刘福强
王海鹏
段武
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Qilu Hospital of Shandong University
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Qilu Hospital of Shandong University
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Abstract

The present disclosure describes a medical dressing having a repair substrate, which includes a middle layer having super-hydrophilicity and having different water absorbability in a longitudinal direction inside, a repair substrate having water-solubility, and an upper bottom layer and a lower bottom layer, the middle layer having an adsorption structure to which the repair substrate is attached, the lower bottom layer having an inner surface, an outer surface, a plurality of through holes, and a super-hydrophobic structure provided on the outer surface, when the medical dressing is applied to a target surface having a liquid layer, liquid on a first region of the target surface corresponding to the through holes is absorbed by the middle layer via the through holes to keep the first region and the through holes dry, and liquid on a second region of the target surface corresponding to the super-hydrophobic structure is at least partially held, and during the absorption of the liquid by the middle layer, the repair substrate is dissolved in the liquid and diffused to the target surface. According to the present disclosure, a medical dressing that can provide a good healing environment and is easily peeled off from a target surface can be provided.

Description

Medical dressing with repair matrix
Technical Field
The invention relates to the technical field of biomedical engineering, in particular to a medical dressing with a repair matrix.
Background
With the development of modern medical technology, people gradually realize that the wound healing is closely related to the environment of the wound in recent years, and the wound is maintained in a moist environment with a proper amount of exudate secreted by the wound part, so that the wound healing is facilitated.
The traditional medical dressing is usually composed of hydrophilic substances such as gauze, bandage and cotton, and is applied on the wound surface to achieve the effects of drainage and the like. For the purpose of keeping a wound clean or needing dressing change, a dressing needs to be replaced periodically, while a traditional medical dressing has strong water absorption and is relatively dry, generally, a proper moist environment cannot be provided for the wound, the healing speed of the wound is affected, the dressing is easy to adhere to the wound, repetitive tissue injury (secondary injury) can be caused to the wound when the dressing is peeled off from the wound, and in addition, fibers of the dressing are easy to fall off and remain on the wound when the dressing is peeled off, foreign body reaction can be caused, and the healing of the wound is affected.
Patent document CN104287890A discloses a wound dressing comprising a liquid permeable layer, a liquid permeable regulation layer, an absorption and retention layer, and a protective layer, which are stacked, wherein the liquid permeable layer has a plurality of through holes, and guides the migration of exudate exuded from a wound into the through holes by capillary action to accumulate the exudate, and the liquid permeable regulation layer keeps the liquid pressure of exudate in the through holes within a predetermined range, thereby keeping the entire surface of a wound surface in a wet environment. Although the wound dressing disclosed in this patent document can keep the wound surface in a moist environment, since the exudate contains substances such as inflammatory mediators and infectious microbes, if an excessive amount of exudate is accumulated on the wound surface for a long time, there is a possibility that a dead space (i.e., a cavity mainly composed of necrotic tissue) of the wound, infection of the wound, and the like occur, and the healing of the wound surface is affected.
Therefore, there is a need for a dressing that provides a good healing environment and is easily peeled from the wound surface.
Disclosure of Invention
In view of the above-described conventional circumstances, an object of the present disclosure is to provide a medical dressing which can provide a good healing environment and can be easily peeled off from a target surface, and a method for producing the same.
To this end, the present disclosure provides a medical dressing having a repair substrate, including an intermediate layer, a water-soluble repair substrate disposed on the intermediate layer, and upper and lower bottom layers respectively disposed on opposite sides of the intermediate layer, the intermediate layer having an ultra-hydrophilic property and an interior having different water absorption properties in a longitudinal direction, the intermediate layer having an adsorption structure in a porous shape to which the repair substrate is attached, the upper bottom layer having a hydrophobic property, the lower bottom layer having an inner surface facing the intermediate layer, an outer surface opposite to the inner surface, a plurality of through holes passing through the inner surface and the outer surface, and an ultra-hydrophobic structure disposed on the outer surface, the ultra-hydrophobic structure including a plurality of micro-scale protrusions arranged at intervals on the outer surface, and nanoparticles disposed on surfaces of the micro-scale protrusions, when the medical dressing is applied to a target surface having a liquid layer, liquid on a first region of the target surface corresponding to the through holes is absorbed by the intermediate layer through the through holes to keep the first region and the liquid on the intermediate layer is at least partially held by the first region and is diffused to the target surface through the micro-scale through holes and dissolved in the liquid in the repair substrate through the through holes.
In the present disclosure, the medical dressing has an upper bottom layer, an intermediate layer and a lower bottom layer, and by setting the upper bottom layer as a hydrophobic layer, it is possible to effectively resist contaminants in the external environment from entering the dressing; the outer surface can be made to have superhydrophobic performance through the superhydrophobic structure arranged on the outer surface of the lower bottom layer, and when the medical dressing is applied to a target surface with a liquid layer, liquid on a second area, corresponding to the superhydrophobic structure, of the target surface can be at least partially retained so that the second area is in a wet environment; the middle layer can absorb liquid on a first area of the target surface corresponding to the through hole by penetrating through the through hole of the lower bottom layer, so that the first area and the through hole are kept dry; in the process that the liquid on the first region is absorbed by the intermediate layer through the through hole, the repair matrix attached to the intermediate layer can be dissolved in the liquid and diffused to the target surface through the liquid; also, by configuring the intermediate layer so that the inside thereof has different water absorbability in the longitudinal direction, it is possible to select a medical dressing having appropriate water absorbability according to the condition of the target surface.
Under the condition, when the target surface is a wound surface, the medical dressing disclosed by the invention is applied to the wound surface, the first area on the wound surface can be in a dry environment through the adsorption of the middle layer on redundant exudate of the wound, the second area can be in a wet state and is not soaked in liquid through the lower bottom layer, in addition, in the process that the middle layer adsorbs the exudate through the through hole, the water-soluble repair matrix is dissolved in the exudate and is diffused to the wound surface through the exudate, the wound surface healing can be facilitated, the adverse effect of a dead cavity on the wound healing can be effectively reduced through the matching of the lower bottom layer and the middle layer, and a good healing environment can be provided for the wound surface; the medical dressing has different water absorbability in the longitudinal direction inside the middle layer, and can select proper water absorbability according to the healing condition of the wound surface, thereby providing a good healing environment for the wound surface; when the medical dressing needs to be peeled off from the wound surface, because the second area is in a humid environment, the super-hydrophobic performance on the surface (namely the outer surface) of the lower bottom layer, which is in contact with the wound, can enable the medical dressing to show anti-adhesion performance on wound secretion, granulation tissues on the surface of the wound and the like, and can reduce the adhesion between the outer surface and the new granulation tissues of the wound, so that the medical dressing is easy to peel off from the wound surface, thereby avoiding secondary damage to the wound; in addition, can effectively resist the pollutant in the external environment and get into the dressing through last bottom, play the barrier effect to reduce the infection risk of wound.
In addition, in the medical dressing according to the present disclosure, optionally, the intermediate layer has a lower surface facing the lower bottom layer and an upper surface facing the upper bottom layer, and the water absorption property of the intermediate layer gradually increases or gradually decreases from the lower surface to the upper surface. Under the condition, when the water absorption of the middle layer is gradually enhanced from the lower surface to the upper surface according to the healing condition of the wound surface, redundant exudate on the wound surface can be quickly absorbed through the middle layer, and the relatively low-hydrophilicity area on the lower layer is beneficial to forming an air cavity for adsorbing liquid and the wound at intervals, so that a good healing environment can be provided for the wound surface at the early stage; when the water absorption of the intermediate layer gradually decreases from the lower surface to the upper surface, the first region on the wound surface can be in a humid ambient air state, thereby providing a good healing environment for the wound surface at the middle and later stages.
Additionally, in the medical dressing to which the present disclosure relates, optionally, the repair matrix comprises a supernatant of mesenchymal stem cells. The supernatant of the mesenchymal stem cells contains a substance capable of promoting wound healing, and in this case, when the repair matrix comes into contact with the wound surface, healing of the wound can be facilitated.
Additionally, in the medical dressing to which the present disclosure relates, optionally, the repair matrix is attached to the absorbent structure in the form of a lyophilized powder. In this case, compared to the stem cell supernatant in a liquid/gel state, the concentration of the effective active cytokine in the unit volume of the stem cell supernatant in the form of lyophilized powder is higher, and the shelf life of the bioactive substance is longer, and when the mesenchymal stem cell supernatant in the form of lyophilized powder is loaded in the middle layer, the medical dressing of the present disclosure can be conveniently stored and clinically applied.
Further, in the medical dressing to which the present disclosure relates, optionally, an area of the open area on the outer surface is no more than 30% of an overall area of the outer surface. In this case, most of the area of the wound surface can be maintained in a moist environment, which can be beneficial to wound healing and also can make the medical dressing easily peel off from the wound surface.
In addition, in the medical dressing according to the present disclosure, optionally, the superhydrophobic structure includes a plurality of micro-scale protrusions arranged on the outer surface at intervals, and nanoparticles disposed on surfaces of the micro-scale protrusions. In this case, by arranging the plurality of micron-sized protrusions and the plurality of nano-particles on the outer surface of the lower bottom layer, when the liquid drop contacts the outer surface, due to the existence of the micron-sized protrusions and the nano-particles, an air film is formed between the liquid drop and the outer surface to block the liquid from wetting the outer surface, so that a super-hydrophobic state can be formed, and the outer surface has super-hydrophobicity.
In addition, in the medical dressing according to the disclosure, optionally, the height of the micrometer-scale protrusions is 20 μm to 150 μm, and the plurality of micrometer-scale protrusions are arranged in an array, and a distance between two adjacent micrometer-scale protrusions is 20 μm to 200 μm. In this case, it is possible to contribute to the improvement of the hydrophobic property of the outer surface, to the maintenance of the second region in a wet environment, and to the easy peeling from the target surface; and the hydrophobic property of each part of the outer surface is relatively uniform, so that the thickness of a liquid layer formed by liquid kept between the second area and the outer surface is generally consistent, the healing speed of the second area is basically consistent, and the wound healing is facilitated.
In addition, in the medical dressing according to the present disclosure, optionally, the nanoparticles have a spherical shape, a conical shape, or a columnar shape, and the particle size of the nanoparticles is 50nm to 1000nm. In this case, it is possible to advantageously improve the hydrophobic property of the outer surface, thereby facilitating maintenance of a wet environment and facilitating peeling.
In addition, in the medical dressing according to the present disclosure, optionally, the superhydrophobic structure is disposed on an inner wall of the through hole. In this case, it is possible to reduce the liquid from hanging on the inner wall of the through hole, which is advantageous for maintaining the dryness in the through hole.
In addition, in the medical dressing according to the disclosure, optionally, the through holes are cylindrical, and the diameter of each through hole is 0.5mm to 3mm, and the distance between two adjacent through holes is 1mm to 5mm. In this case, it can be facilitated for the intermediate layer to absorb the liquid of the target surface through the through-hole.
According to the present disclosure, a medical dressing that can provide a suitable healing environment for a wound surface and is easily peeled off from the wound surface can be provided.
Drawings
Fig. 1 is a schematic diagram illustrating a first embodiment of a medical dressing according to examples of the present disclosure.
Fig. 2 is a schematic cross-sectional view illustrating the medical dressing shown in fig. 1.
Fig. 3 is a schematic, fragmentary view illustrating a first perspective of the medical dressing shown in fig. 1.
Fig. 4 is a fragmentary schematic view illustrating a second perspective of the medical dressing shown in fig. 1.
Fig. 5 is a schematic diagram illustrating a superhydrophobic structure according to an example of the present disclosure.
Fig. 6 is a schematic diagram illustrating a second embodiment of a medical dressing according to examples of the present disclosure.
Fig. 7 is a schematic diagram illustrating a method of making a medical dressing according to examples of the present disclosure.
Fig. 8 is a schematic diagram illustrating a method of making a repair matrix according to examples of the present disclosure.
Description of reference numerals:
1, 8230, a medical dressing, 10, 8230, a lower bottom layer, 11, 8230, an inner surface, 12, 8230, an outer surface, 13, 8230, a through hole, 14, 8230, a super-hydrophobic structure, 141, 8230, a micron-sized protrusion, 142, 8230, a nano-particle, 20, 8230, a middle layer, 30, 8230, an upper bottom layer, 40, 8230, a protective film, 50, 8230, a second protective film, 9, 8230, a wound surface, 90, 8230, a liquid layer, S1, 8230, a first area, S2, 8230and a second area.
Detailed Description
All references cited in this disclosure are incorporated by reference in their entirety as if fully set forth. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.
Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the following description, the same components are denoted by the same reference numerals, and redundant description thereof is omitted. The drawings are schematic and the ratio of the dimensions of the components and the shapes of the components may be different from the actual ones.
The present disclosure relates to a medical dressing having a repair matrix that can be used to protect a target surface. The medical dressing with the repair matrix of the present disclosure may be referred to simply as a "medical dressing" or "dressing," and may also be referred to as a water-absorbing dressing, a wound dressing, and the like. With the medical dressing according to the present disclosure, it is possible to suck up excess liquid from a target surface, provide a suitable wet environment for the target surface, and easily peel off from the target surface.
In the present disclosure, the target surface may be a wound surface. Among them, the wound surface is a lesion caused by a normal skin (tissue) injury, and may be a wound caused by a condition such as a scald, an abrasion, a cut, a sprain, an ulcer, a frostbite, or the like. The wound surface may also be referred to as a wound or trauma. In other examples, the target surface may also be other surfaces, such as a skin surface. It should be noted that the medical dressing according to the present disclosure may also be applied as a protective layer to, for example, a semi-healed wound surface that has scabbed and dried.
When the medical dressing is applied to a wound surface, a liquid layer formed by exudates secreted by the wound surface exists in at least part of area between the wound surface and the medical dressing, so that a proper humid environment is provided for the wound surface, and in addition, a repair matrix carried on the medical dressing can be transferred to the wound surface, so that a good healing environment can be provided for the wound; when the wound surface is required to be stripped, the super-hydrophobic outer surface can reduce the adhesion with the granulation tissue of the wound, so that the wound surface is easy to strip from the wound surface, and secondary damage (namely secondary damage) to the wound is avoided. It should be noted that, in the present disclosure, providing a suitable moist environment/healing environment for a wound surface means that the wound surface can be moistened without being soaked in a liquid by the medical dressing of the present disclosure.
Hereinafter, a medical dressing according to the present disclosure will be described with reference to the drawings, taking as an example a wound surface having a exuded liquid layer as a target surface.
Fig. 1 is a schematic diagram illustrating a first embodiment of a medical dressing 1 according to examples of the present disclosure. Fig. 2 is a schematic sectional view showing the medical dressing 1 shown in fig. 1. Fig. 3 is a schematic split view showing a first perspective of the medical dressing 1 shown in fig. 1. Fig. 4 is a schematic split view showing a second perspective of the medical dressing 1 shown in fig. 1. In fig. 2, the arrows schematically indicate the moving direction of the exudate. In addition, it should be noted that the first viewing angle is a viewing angle viewed obliquely downward, and the second viewing angle is a viewing angle viewed obliquely upward.
In some examples, the medical dressing 1 may include a lower bottom layer 10, an intermediate layer 20, and an upper bottom layer 30 (see fig. 1) disposed in a sequential stack. The upper substrate 30 may be hydrophobic, the outer surface 12 of the lower substrate 10 may be superhydrophobic, the intermediate layer 20 may be superhydrophilic, the lower substrate 10 may be in contact with the wound bed 9 when the medical dressing 1 is applied to a target surface (the wound bed 9 having a exudate layer 90), and the intermediate layer 20 may be used to draw fluid from the wound bed 9 (see fig. 2).
In some examples, the medical dressing 1 may further include a middle layer 20, a water-soluble repair substrate disposed on the middle layer 20, and an upper bottom layer 30 and a lower bottom layer 10 (see fig. 1) disposed on opposite sides of the middle layer 20, respectively. In this case, when the medical dressing 1 is applied to the wound surface 9, the repair matrix can be dissolved in the exudate during the process of the middle layer 20 absorbing the exudate on the wound surface 9 and can be diffused to the wound surface 9 through the exudate for repair.
In some examples, the lower base layer 10 may have an inner surface 11 facing the intermediate layer 20, an outer surface 12 opposite the inner surface 11, and a plurality of through-holes 13 (see fig. 2) passing through the inner and outer surfaces 11, 12. The intermediate layer 20 can absorb liquid from the wound bed 9 through the through-openings 13.
In some examples, the lower base layer 10 may also have superhydrophobic structures 14 (described later) disposed on the outer surface 12. This can make the outer surface 12 super-hydrophobic. In the present disclosure, superhydrophobicity means that the contact angle of a micro water drop on the surface is greater than 150 ° and the rolling angle is less than 10 °. That is, by disposing the superhydrophobic structure 14 on the outer surface 12, the contact angle of the micro water drop on the outer surface 12 can be made larger than 150 °, and the rolling angle is less than 10 °.
In some examples, the region of the target surface corresponding to the through hole 13 is a first region S1, and the region corresponding to the superhydrophobic structure 14 is a second region S2, see fig. 2, in which parts of the first region S1 and the second region S2 are schematically labeled.
In some examples, when the medical dressing 1 is applied to a target surface having the liquid layer 90, liquid on a first area S1 of the target surface corresponding to the through-hole 13 is absorbed by the intermediate layer 20 via the through-hole 13 to keep the first area S1 and the through-hole 13 dry, and liquid on a second area S2 of the target surface corresponding to the superhydrophobic structure 14 is at least partially retained. In this case, when the target surface is the wound surface 9, the medical dressing 1 is applied to the wound surface 9, the first area S1 on the wound surface 9 can be in a dry environment through the adsorption of the intermediate layer 20 to the excess exudate of the wound, a part of the exudate can be maintained between the outer surface 12 and the second area S2 through the super-hydrophobic outer surface 12 of the lower bottom layer 10, the second area S2 is in a moist tissue contact environment, and therefore not only can the adverse effect of dead cavities on wound healing be effectively avoided, but also a good healing environment can be provided for the wound surface 9; when the medical dressing 1 needs to be peeled off from the wound surface 9, because the second area S2 is in a humid environment, the superhydrophobic performance on the surface (namely the outer surface 12) of the lower bottom layer 10, which is in contact with the wound, can enable the lower bottom layer to show anti-adhesion performance to wound secretions, granulation tissues on the wound surface and the like, and can reduce adhesion between the outer surface 12 and the granulation tissues newly grown in the wound, so that the medical dressing is easy to peel off from the wound surface 9, thereby avoiding secondary damage to the wound, and because of the interval of the lower bottom layer 10, dressing fibers of the middle layer 20 are not easy to fall off to the wound surface 9, and foreign body reaction of the wound can be effectively reduced.
In some examples, the through-hole 13 may be cylindrical. That is, the through-hole 13 has a uniform aperture diameter at the inner surface 11 and the outer surface 12. In this case, it can be facilitated that the intermediate layer 20 absorbs the liquid of the target surface through the through-holes 13.
In some examples, the diameter of the through-hole 13 may be 0.5mm to 3mm. In this case, it is possible to facilitate the intermediate layer 20 to absorb the liquid on the target surface from the through-holes 13 at an appropriate rate (see fig. 2, arrows schematically indicate the moving direction of the exudate during absorption of the exudate by the intermediate layer 20) to maintain the dryness of the through-holes 13 and the first region S1.
In some examples, the pitch between two adjacent through holes 13 may be 1mm to 5mm. In some examples, the plurality of through holes 13 may be arranged in an array (see fig. 4). In this case, the unperforated regions (i.e., the regions provided with the superhydrophobic structures 14) on the outer surface 12 are also uniformly distributed, thereby enabling easy peeling.
In some examples, the area of the open area on the outer surface 13 is no greater than 30% of the total area of the outer surface 13. That is, the plurality of through-holes 3 occupy an area on the outer surface 13 of not more than 30% of the total area of the outer surface 13. In this case, a large area of the wound surface 9 corresponding to the non-perforated area of the outer surface 13 can be maintained in a moist environment, which can facilitate healing of the wound surface 9 and also enable the medical dressing 1 to be easily peeled off from the wound surface 9.
Fig. 5 is a schematic diagram illustrating a superhydrophobic structure 14 according to an example of the present disclosure. Fig. 5 is an enlarged view of a region a in fig. 1.
In some examples, a superhydrophobic structure 14 is disposed on the outer surface 12. It will be appreciated that the superhydrophobic structure 14 is an unperforated region disposed on the outer surface 12.
In some examples, the superhydrophobic structure 14 may include a plurality of micro-scale protrusions 141 arranged on the outer surface 12 at intervals, and nanoparticles 142 disposed on surfaces of the micro-scale protrusions 141 (see fig. 5). In this case, by providing the plurality of micro-scale protrusions 141 and the nano-particles 142 on the outer surface 12 of the lower substrate 10, when the liquid drop contacts the outer surface 12, due to the micro-scale protrusions 141 and the nano-particles 142, an air film is formed between the liquid drop and the outer surface 12 to prevent the liquid from wetting the outer surface 12, so that a super-hydrophobic state can be formed, and the outer surface 12 has super-hydrophobicity; when the medical dressing 1 is attached to the wound surface 9, a liquid layer 90 (see fig. 2) formed by exudate secreted by the wound surface 9 is formed between the outer surface 12 of the lower bottom layer 10 and the wound surface 9, so that the wound surface 9 is in a moist tissue contact environment, and the healing of the wound surface 9 is facilitated; when it is desired to peel the medical dressing 1 from the wound bed 9, adhesion of the outer surface 12 to the granulation tissue of the wound can be reduced due to the presence of the liquid layer 90, so that the medical dressing 1 can be easily peeled from the wound bed 9.
In the present disclosure, the superhydrophobic structure 14 including the micro-scale protrusions 141 and the nanoparticles 142 may also be referred to as a micro-nano structure.
In some examples, the micro-scale protrusions 141 may be in the shape of a mastoid, a cone, or a cylinder. In some examples, the height of the micro-scale protrusions 141 is 20 μm to 150 μm. In this case, it is possible to advantageously improve the hydrophobic property of the outer surface 12, thereby facilitating maintenance of a wet environment, and easy peeling.
In some examples, the micro-scale protrusions 141 may be arranged in a matrix. In some examples, the pitch of the adjacent two micro-scale protrusions 141 may be 20 μm to 200 μm. In this case, the hydrophobic properties of the outer surface 12 are relatively uniform throughout, and the thickness of the liquid layer 90 formed by the liquid held between the second region S2 and the outer surface 12 can be substantially uniform, so that the healing rate of the second region S2 is substantially uniform, which is beneficial for the healing of the wound surface 9.
In some examples, a ratio of a pitch of two adjacent micro-scale protrusions 141 to a height of the micro-scale protrusions 141 may be 1 to 1.3. In this case, the liquid droplets can be conveniently rolled among the plurality of micro-scale protrusions 141, and the rolling angle on the outer surface 12 is reduced, thereby being advantageous to improve the hydrophobic property of the outer surface 12. For example, the ratio of the pitch of two adjacent micro-scale protrusions 141 to the height of the micro-scale protrusions 141 may be 1.
In some examples, the nanoparticles 142 may be spherical, pyramidal, cylindrical, or irregular cubic. This can contribute to further improving the hydrophobic property of the outer surface 12, thereby facilitating maintenance of a wet environment and facilitating peeling.
In some examples, the nanoparticles 142 may range in size from 50nm to 1000nm. The particle size range refers to the diameter of the nanoparticles 142 when they are spherical, and refers to the equivalent diameter of the three-dimensional structure when they are not spherical.
In some examples, the number of nanoparticles 142 may be plural, and the particle diameters and shapes of the plural nanoparticles 142 may be the same or different (see fig. 5).
In some examples, the superhydrophobic structure 14 disposed on the outer surface 12 can be formed by way of laser machining. Specifically, a femtosecond laser is used to perform laser etching on the outer surface 12 of the lower bottom layer 10 to form a dual-scale micro-nano structure, that is, a plurality of micron-scale protrusions 141 and a plurality of nano-particles 142 formed on the surfaces of the micron-scale protrusions 141 are formed on the outer surface 12, and after the laser etching, the outer surface 12 can be cleaned to remove surface impurity particles, so as to obtain the outer surface 12 provided with the superhydrophobic structure 14. It should be noted that, limited by the existing processing precision, when the micro-nano structure is prepared, the prepared micro-scale protrusions 141 and/or nano-particles 142 may not form a completely regular shape on a micro-scale layer, and the mastoid-like structure with a substantially regular outline and a certain height may be formed to play a role of water repellency.
In some examples, by disposing the superhydrophobic structure 14 on the outer surface 12, a contact angle of a micro water drop of the outer surface may be greater than 150 ° and a rolling angle below 10 °. In this case, the superhydrophobic structure 14 disposed on the outer surface 12 can improve hydrophobicity, so that the outer surface has superhydrophobic performance, thereby facilitating maintenance of a moist environment between the outer surface 12 and the wound surface 9, and facilitating peeling of the medical dressing 1 from the wound surface 9.
In some examples, the contact interface wetting state between the superhydrophobic structure 14 and the water-based microdroplets is a stable Cassie-Baxter wetting state, whose stability appears as: 8 mu L of water-based micro-droplets are dropped on the surface of the super-hydrophobic structure 14 at the height of 0.3m in a free-fall manner, and the bouncing behavior is shown.
In some examples, the superhydrophobic structure 14 can be integrally formed with the outer surface 12. In some examples, the material of the superhydrophobic structure 14 may be consistent with the material of the lower substrate layer 10. That is, the superhydrophobic structure 14 can be engraved on the outer surface 12 directly by means of, for example, laser machining. In this case, it can be facilitated to prepare the lower base layer 10 having the superhydrophobic structure 14, and it can be advantageous to maintain the hydrophobicity of the outer surface 12.
In some examples, a superhydrophobic structure 14 may also be disposed on an inner wall of the through-hole 13. In this case, the liquid can be prevented from being caught on the inner wall of the through hole 13, which is advantageous for maintaining the dryness of the inside of the through hole 13.
In some examples, the thickness of the lower base layer 10 may be 0.1mm to 2mm. It should be noted that, in the present disclosure, the thickness of the lower base layer 10 is the thickness of the whole including the micrometer-scale protrusions 141 and the nanoparticles 142. In this case, the lower base layer 10 is moderate in thickness and can maintain good air permeability, and can facilitate the middle layer 20 to absorb liquid from the target surface through the through-holes 13. In some examples, the thickness of the lower base layer 10 may be preferably 0.1mm to 1mm.
In some examples, the lower substrate 10 may be composed of a hydrophobic material. In other words, the lower layer 10 may have hydrophobicity. That is, the contact angle on the inner surface 11 of the lower base layer 10 and the through hole 13 may be greater than 90 °. In this case, it can be convenient to maintain a moist environment between the outer surface 12 and the wound bed 9.
For example, in some examples, the material of the lower base layer 10 may be silicone. In some examples, the lower base layer 10 may be a silicone rubber film, which may also be referred to as a PDMS (polydimethylsiloxane) film. In this case, the lower bottom layer 10 is soft and has good biocompatibility and air permeability, and no irritation to human tissues, which is beneficial to healing of the wound surface 9.
In some examples, the intermediate layer 20 may absorb liquid. In some examples, the liquid absorbed by the intermediate layer 20 may adhere to the intermediate layer 20, i.e., the liquid absorbed by the intermediate layer 20 may remain in the intermediate layer 20 without diffusing outward.
In this case, the liquid on the first region S1 of the target surface corresponding to the through-hole 13 can be absorbed by the intermediate layer 20 via the through-hole 13, and the liquid in the through-hole 13 can also be absorbed by the intermediate layer 20, so that the first region S1 and the inside of the through-hole 13 can be kept dry, thereby making it possible to suppress adverse effects on wound healing such as dead space and the like, and provide a good healing environment for wound surface 9 healing. Wherein, as will be understood by those skilled in the art, keeping the first region S1 and the through hole 13 dry may refer to a relatively dry environment; specifically, the first region S1 and the inside of the through-hole 13 can be kept dry by the absorption of the exudate by the intermediate layer 20 in a normal case. It should be noted that, in some cases, due to the spacing of the lower bottom layer 10, the first area S1 is not in contact with the middle layer 20, and a part of the liquid on the surface of the first area S1 (for example, a part of the liquid on the first area S1 that is not in the through hole 13) may not be absorbed by the middle layer 20 in time, and will still be absorbed by the middle layer 20 as the part of the liquid increases and flows to the vicinity of the through hole 13. This case also falls within the scope of "the first region S1 and the inside of the through-hole 13 are kept dry" in the present disclosure, that is, at least the dry atmosphere inside the through-hole 13 can be maintained by the adsorption of the intermediate layer 20.
That is, in the present disclosure, the adsorption by the intermediate layer 20 can not only maintain the wettability of the wound surface 9, but also effectively avoid the adverse effect of the dead space on the wound healing. In addition, in the present disclosure, the intermediate layer 20 can absorb excessive exudate, so that the wound surface 9 is wet but not soaked in liquid, and a good healing environment is provided for the wound surface 9.
In some examples, the intermediate layer 20 may include a hydrophilic material. This can make the intermediate layer 20 hydrophilic.
In some examples, the intermediate layer 20 may have super-hydrophilicity. That is, the contact angle of a water droplet with the intermediate layer 20 is close to 0 °, and the intermediate layer 20 is very easily wetted. In this case, the intermediate layer 20 can sufficiently absorb the excess exudate on the wound surface 9, and the exudate is easy to diffuse in the intermediate layer 20 after entering the intermediate layer 20, which is beneficial to improving the liquid absorption performance of the intermediate layer 20. In the present disclosure, superhydrophilic means that the contact angle of the surface with a drop of water is not more than 5 °. That is, the contact angle of the water droplet with the surface of the intermediate layer 20 having super hydrophilicity may be not more than 5 °. For example, the contact angle of the water droplet with the surface of the intermediate layer 20 having super hydrophilicity may be 5 °,4 °,3 °,2 °,1 °, 0.8 °, 0.6 °, 0.5 °, 0.3 °, 0.2 °, or 0.1 °.
In some examples, the middle layer 20 may also include highly hydrophilic fibers. For example, in some examples, the material of the intermediate layer 20 may include sodium carboxymethyl cellulose. In this case, on the one hand, the intermediate layer 20 can be made super-hydrophilic, and on the other hand, the water retention effect of the intermediate layer 20 can be enhanced.
In some examples, the intermediate layer 20 may also include cotton batting. In some examples, the intermediate layer 20 may be a sponge sheet, a mesh nonwoven, or a medical cotton pad including cotton wool, or the like. In this case, the intermediate layer 20 has a high hydrophilicity and is soft in texture, can absorb excess exudate, and can provide a good healing environment for the wound bed 9.
In some examples, the thickness of the intermediate layer 20 may be 0.5mm to 5mm. In this case, the intermediate layer 20 has good air permeability and water absorption, can contribute to providing a good healing environment, and can give the medical dressing 1 as a whole good mechanical strength by the provision of the thickness of each functional layer. In some examples, the thickness of the intermediate layer 20 may be preferably 1mm to 1.5mm. In this case, the air permeability of the entire medical dressing 1 can be further optimized while having good water absorption properties.
In some examples, the interior of the intermediate layer 20 may have different water absorption properties. Specifically, the inside of the intermediate layer 20 may have different water absorbability in the longitudinal direction. The healing environment required for the wound surface 9 at different stages differs (described later), and in this case, by configuring the intermediate layer 20 so that the inside thereof has different water absorbability in the longitudinal direction, it is possible to select appropriate water absorbability according to the healing condition of the wound surface 9, providing a good healing environment for the wound surface 9.
In some examples, the middle layer 20 has a lower surface facing the lower bottom layer 30 and an upper surface facing the upper bottom layer 10. The longitudinal direction may refer to a direction orthogonal to the lower and upper surfaces.
In some examples, the water absorption of the intermediate layer 20 may gradually increase from the lower surface to the upper surface. For convenience of description, a portion of the middle layer 20 relatively adjacent to the upper bottom layer 30 is referred to as an upper layer, and a portion relatively adjacent to the upper bottom layer 10 is referred to as a lower layer (it does not mean that the middle layer 20 of the present disclosure includes only two layers with a well-defined interval). In the early stage of wound occurrence, the wound surface 9 secretes more exudate, in this case, when the medical dressing 1 is applied to the wound surface 9 in the early stage, the exudate of the wound surface 9 moves from the through hole 13 to be in contact with the lower layer of the intermediate layer 20 and is absorbed by the lower layer, compared with the intermediate layer 20 with uniform water absorption of the upper layer and the lower layer, because the water absorption of the upper layer of the intermediate layer 20 is greater than that of the lower layer in this example, most of the exudate in the lower layer tends to diffuse towards the upper layer, and only a small part of the exudate laterally diffuses in the lower layer, at this time, the unsaturated lower layer continues to rapidly absorb the exudate in the first region S1 and the through hole 13, thereby, the excess exudate on the wound surface 9 can be rapidly absorbed through the intermediate layer 20, and the relatively low-hydrophilic region of the lower layer helps to form an air cavity for adsorbing the liquid and the wound, so that good environmental healing can be provided for the wound surface 9 in the early stage.
In other examples, the water absorption of the intermediate layer 20 may gradually decrease from the lower surface to the upper surface. In the middle and later stages of wound formation, the wound surface 9 secretes less exudate, and a part of the area on the wound surface 9 may have scab, in this case, by configuring the water absorption property of the lower layer of the intermediate layer 20 to be stronger than the water absorption property of the upper layer, when the medical dressing 1 is applied to the wound surface 9 in the middle and later stages, the exudate on the wound surface 9 is absorbed by the lower layer of the intermediate layer 20 through the through holes 13, most of the exudate in the lower layer tends to be diffused laterally inside the lower layer, and most of the exudate is kept in the lower layer of the intermediate layer 20, so that the first area S1 on the wound surface 9 can be in a humid ambient air state, thereby, a good healing environment can be provided for the wound surface 9 in the middle and later stages.
In some examples, the water absorption of the intermediate layer 20 may vary in a gradient as it gradually increases or decreases from the lower surface to the upper surface. Specifically, taking as an example that the thickness of the intermediate layer 20 is 3mm and the water absorption property of the intermediate layer 20 is gradually increased from the lower surface to the upper surface, the intermediate layer 20 is divided into 3 divided layers having a thickness of 1mm according to the thickness, the first layer, the second layer, and the third layer are provided in this order from the lower surface to the upper surface, the water absorption property of the inside of each divided layer is uniform, and the water absorption property of each divided layer satisfies: the water absorption of the first layer is less than the water absorption of the second layer is less than the water absorption of the third layer. Thereby, it is possible to facilitate the preparation of the intermediate layer 20 having different water absorbability.
In some examples, the early stage of wound appearance may refer to the first three days of wound appearance, and the mid-late stage may refer to a period of three days after wound appearance. Of course, since each patient has a different body constitution, the recovery degree of the wound surface 9 may be different even after the same time, and the configuration of the intermediate layer 20 may be selected according to the amount of exudate secreted from the wound. Specifically, the healing of the wound can be generally divided into four stages, namely, a coagulation stage, an inflammation stage, a repair stage and a maturation stage, and the early stage of the wound occurrence in the present disclosure may refer to a stage in which the wound is in the coagulation stage and/or the inflammation stage, and the middle and later stage may refer to a stage in which the wound is in the repair stage and/or the maturation stage.
In some examples, the middle layer 20 may include an upper layer relatively close to the upper bottom layer 30, and a lower layer relatively close to the upper bottom layer 10. In some examples, the water absorption of the upper layer may be greater than the water absorption of the lower layer. This provides a good healing environment for the wound surface 9 at an early stage. In other examples, the water absorption of the upper layer may be less than the water absorption of the lower layer. Thereby, a good healing environment can be provided for the wound surface 9 at the middle and later stages.
In some examples, the middle layer 20 may also include a transition layer between the upper and lower layers. The water absorption of the transition layer is between the water absorption of the upper layer and the water absorption of the lower layer.
In some examples, the portions of the intermediate layer 20 having different water absorptions may be composed of different materials, or have different structures. This makes it possible to provide different water absorptions in the intermediate layer 20. In some examples, the water absorbency can be adjusted by varying the degree of densification of the network structure within the intermediate layer 20. For example, the water absorption of the corresponding region can be improved by increasing the degree of densification of the network structure.
In some examples, the intermediate layer 20 may have an adsorption structure. This enables adsorption of the repair substrate.
In some examples, the adsorption structure may be porous and the repair matrix may be attached to the adsorption structure. Wherein, the repair matrix can be a water-soluble material. In this case, in the process of adsorbing the exudate by the intermediate layer 20 through the through holes 13, the water-soluble repair matrix is dissolved in the exudate and is diffused to the wound surface 9 through the exudate, so that the healing of the wound surface 9 can be facilitated. That is, the repair matrix may be releasably attached to the absorbent structure. The repair matrix may be attached to the absorbent structure when it is not in contact with the liquid, and may dissolve in the liquid and undergo molecular diffusion movement within the liquid (i.e., be released by the absorbent structure) when it is in contact with the liquid.
In some examples, the adsorbent structure may be disposed on a surface of the middle layer 20 relatively close to the lower substrate 10. For example, the adsorption structure may be a plurality of groove structures disposed on a surface of the middle layer 20 relatively close to the lower substrate 10. Thereby, the repair substrate can be accommodated and adsorbed by the groove structure.
In some examples, the repair matrix may include mesenchymal stem cells and/or derivatives of mesenchymal stem cells. For example, in some examples, the repair matrix may include a supernatant of mesenchymal stem cells. The supernatant of the mesenchymal stem cells contains a substance capable of promoting wound healing, in which case healing of the wound can be facilitated when the repair matrix is in contact with the wound bed 9.
In some examples, mesenchymal stem cell-derived exosomes may be included in the supernatant of mesenchymal stem cells. Among them, exosomes are extracellular vesicles containing complex RNAs and proteins secreted by cells. Under the condition, the exosome derived from the mesenchymal stem cells can promote the healing of the wound surface 9 by using the paracrine effect, inhibit the inflammatory reaction of the wound surface 9, promote the angiogenesis, improve the extracellular matrix environment, mobilize the cells of the organism to migrate to the damaged part, and repair the wound surface 9.
In some examples, one or more of vascular endothelial growth factor, epidermal growth factor, transforming growth factor-beta, liver growth factor, superoxide dismutase, interleukin-6, collagen, fibronectin, and platelet-derived factor may also be included in the supernatant of the mesenchymal stem cells. In this case, the healing of the wound can be advantageously promoted by the prosthetic matrix.
In some examples, the supernatant of the mesenchymal stem cells may include one or more of exosomes of mesenchymal stem cells, vascular endothelial growth factor, epidermal growth factor, transforming growth factor-beta, liver growth factor, superoxide dismutase, interleukin-6, collagen, fibronectin, and platelet-derived factor. In this case, the repair ability of the repair matrix can be further improved, thereby promoting wound healing.
The present disclosure is not limited thereto, and the corresponding repair matrix may be selected according to the actual condition of the wound surface 9. For example, in some examples, the repair matrix may also include other components that aid in wound healing. For example, the repair matrix may also include hemostatic powders and the like.
In some examples, the mesenchymal stem cell may be an umbilical cord mesenchymal stem cell, a bone marrow mesenchymal stem cell, or an adipose mesenchymal stem cell. The repair matrix may include a plurality of mesenchymal stem cells and/or derivatives of mesenchymal stem cells. That is, in some examples, the repair matrix may include derivatives of one or more of umbilical cord mesenchymal stem cells, bone marrow mesenchymal stem cells, and adipose mesenchymal stem cells. Under the condition, various mesenchymal stem cells and derivatives thereof can be beneficial to wound healing, have rich sources, and can conveniently adjust the components of the repair matrix according to actual needs.
In some examples, the repair matrix may be attached to the adsorption structure in the form of a lyophilized powder. In this case, the concentration of the effective active cytokine per unit volume of the stem cell supernatant in the form of lyophilized powder is higher and the shelf life of the bioactive substance is longer compared to the stem cell supernatant in the liquid/gel state, and when the mesenchymal stem cell supernatant in the form of lyophilized powder is loaded on the intermediate layer 20, the medical dressing 1 of the present disclosure can be conveniently stored and clinically applied.
In some examples, the repair matrix may include umbilical cord mesenchymal stem cell exosomes, bone marrow mesenchymal stem cells, and/or adipose mesenchymal stem cell-derived exosomes.
In some examples, taking a lyophilized powder of the repair matrix including umbilical cord mesenchymal stem cell supernatant as an example, the preparation method may include: taking Wharton's jelly on an umbilical cord, and performing in vitro culture to obtain umbilical cord mesenchymal stem cells; subculturing; after culturing for a preset time, collecting cell supernatant and centrifuging to obtain supernatant containing umbilical cord mesenchymal stem cells; and adding a freeze-drying protective agent into the supernatant containing the umbilical cord mesenchymal stem cells, and freeze-drying to obtain the freeze-dried powder of the repair matrix comprising the umbilical cord mesenchymal stem cell supernatant. Wherein the Wharton's jelly is the gel filling between the amniotic membrane of umbilical cord and blood vessel. Therefore, the lyophilized powder of the repair matrix comprising the umbilical cord mesenchymal stem cell supernatant with good repair effect can be obtained. Of course, the embodiment is not limited thereto, and the lyophilized powder of the repair matrix including the umbilical cord mesenchymal stem cell supernatant may be obtained in other ways, which should not be construed as limiting.
In some examples, in the preparation method of the lyophilized powder of the repair matrix comprising the umbilical cord mesenchymal stem cell exosomes, umbilical cord mesenchymal stem cells obtained by extracorporeal culture are recorded as P0 generation, and can be subcultured for 3-5 times when subcultured is carried out, and the culture is continued by replacing a blank serum-free culture medium after P3-P5 generation.
In some examples, in the method of preparing a lyophilized powder of a repair matrix including umbilical cord mesenchymal stem cell exosomes, the culturing for a predetermined time may refer to culturing for 24 to 96 hours.
In some examples, in the preparation method of the lyophilized powder of the repair matrix including the umbilical cord mesenchymal stem cell exosomes, the supernatant containing the umbilical cord mesenchymal stem cell exosomes may be further centrifuged at a rotation speed of 800rpm/min to 2000rpm/min for 5min to 15min at a temperature of 2 ℃ to 6 ℃, and the supernatant is taken and added with a lyoprotectant for freeze-drying. Under the condition, impurities can be further removed, and the supernatant containing the umbilical cord mesenchymal stem cell exosomes with high purity can be obtained.
In some examples, the repair matrix in powder form has a density of 0.5mg/cm2 to 5mg/cm2 on the surface of the middle layer 20 relatively close to the lower bottom layer 10. In this case, healing of the wound surface 9 can be facilitated.
In some examples, the repair matrix in powder form may be sprinkled evenly over the surface of the middle layer 20 adjacent to the lower bottom layer 10 and adsorbed by the middle layer 20. In other examples, the density of the repair matrix may be higher on a region of the surface of the intermediate layer 20 relatively close to the lower base layer 10 opposite to the through-holes 13 than other regions on the surface. Therefore, the repair matrix can be conveniently diffused to the wound surface 9 through the exudate in the process that the middle layer 20 absorbs the exudate from the through hole 13 so as to repair the wound surface 9.
In other examples, the intermediate layer 20 may be immersed in a supernatant containing the exosomes of umbilical cord mesenchymal stem cells, and the intermediate layer 20 loaded with the supernatant may be freeze-dried, so that the repair matrix is releasably attached to the intermediate layer 20 and uniformly distributed in the intermediate layer 20.
In some examples, the medical dressing 1 may be applied to the wound bed 9 prior to applying the medical dressing 1 to the wound bed 9, and then the medical dressing 1 is applied to the wound bed 9. The components of the medicine can be the same as those of the repairing matrix, and can also be other components capable of promoting wound healing. In this case, the repair matrix can be used in combination with a drug to further improve the ability of the repair to the wound, thereby promoting wound healing.
For example, in some examples, the composition of the drug may also include exosomes of umbilical cord mesenchymal stem cells, and the drug may also be present in the form of a lyophilized powder, in which case the drug may be uniformly sprinkled on the wound surface 9 before the medical dressing 1 is applied to the wound surface 9. Under the condition, the exosome of the umbilical cord mesenchymal stem cells can exert the biological effect of the umbilical cord mesenchymal stem cells, and the wound surface 9 is promoted to heal.
In some examples, the upper substrate 30 may include a hydrophobic material. This can make the top sheet 30 hydrophobic. In this case, the upper bottom layer 30 can effectively resist the contaminants in the external environment from entering the dressing 1, and can play a role of a barrier, so that the infection risk of the wound surface 9 is reduced.
In some examples, the superhydrophobic structure 14 may be provided on a surface of the upper substrate 30 facing the middle layer 20 and on a surface opposite to the surface, respectively. In this case, the hydrophobicity of the two surfaces of the upper bottom layer 30 can be enhanced, so that the outward evaporation of the exudate in the middle layer 20 can be inhibited, and a proper moist environment can be provided for the wound surface 9; in addition, pollutants in the external environment, particularly substances (particularly liquid) possibly carrying bacteria, can be effectively prevented from entering the medical dressing 1 and moving to the wound surface 9, and the infection risk of the wound surface 9 is reduced.
In some examples, the upper substrate layer 30 may have a thickness of 0.2mm to 1mm. In this case, the upper and lower layers 30 have good air permeability and strong mechanical strength, and can effectively play a barrier role and provide a good healing environment for the wound surface 9. In some examples, the upper substrate layer 30 may preferably have a thickness of 0.2mm to 0.5mm. In this case, the breathability of the upper chassis layer 30 can be further improved while functioning as a barrier.
In some examples, the material of the upper layer 30 may be silicone. That is, the upper layer 30 may be a silicone rubber film, which may also be referred to as a PDMS (polydimethylsiloxane) film. In this case, the upper and lower layers 30 are soft and have good air permeability, and can provide a good healing environment for the wound surface 9.
In some examples, the lower base layer 10, the middle layer 20, and the upper base layer 30 may be sheet-like. That is, the medical dressing 1 may be in the form of a sheet. In this case, it can be facilitated to cover the target surface.
In some examples, adjacent two layers of the upper bottom layer 30, the middle layer 20, and the lower bottom layer 10 are bonded to each other by an adhesive, and no adhesive is provided in a region of the middle layer 20 corresponding to the through-hole 13. In this case, the layers can be tightly bonded to each other, and the intermediate layer 20 can absorb liquid from the target surface through the through-holes 13.
In some examples, the outer peripheral zones between the middle layer 20 and the lower base layer 10 are joined to each other by an adhesive.
In some examples, the medical dressing 1 may be in the form of a long roll. The medical dressing 1 may be cut to a desired size (e.g., a shape that can cover the wound bed 9) for use.
In some examples, the medical dressing 1 may have a length of 20mm to 120mm and a width of 20mm to 120mm. In this case, it can be fitted to the small wound surface 9 and is portable. The present disclosure is not limited thereto, and the size of the medical dressing 1 may also be adjusted according to actual needs. For example, when the area of the target surface is large, it may be protected with the medical dressing 1 capable of covering the size of the target surface.
In some examples, the medical dressing 1 may be attached to the wound bed 9 by medical tape. Or both ends of the upper bottom layer 30 can be directly extended outwards, and the inner walls of both ends of the upper bottom layer 30 extending outwards are provided with adhesives, so that a form of a band-aid can be formed, and the medical dressing 1 can be attached to the wound surface 9.
In some examples, the medical dressing 1 may have a use period of 0.5 to 3 days. In some examples, the medical dressing 1 preferably has a lifetime of 12 to 36 hours. The term of use refers to the length of time that the medical dressing 1 is applied to the target surface. In this case, it is possible to contribute to maintaining good air permeability and provide a suitable healing environment for the wound surface 9.
Fig. 6 is a schematic diagram illustrating a second embodiment of a medical dressing 1 according to examples of the present disclosure.
In some examples, the medical dressing 1 further includes a protective film 40 (see fig. 6) that releasably covers the outer surface 12. In this case, the outer surface 12 can be maintained in a clean state before use by providing the protective film 40, and when it is necessary to attach the medical dressing 1 to the wound surface 9, the protective film 40 may be peeled off from the outer surface 12.
In some examples, the shape of the protective film 40 may conform to the shape of the lower base layer 10. For example, in the embodiment where the lower base layer 10 is sheet-shaped, the protective film 40 may also be sheet-shaped, and the area of the protective film 40 in sheet shape is not smaller than the area of the outer surface 12 of the lower base layer 10.
In some examples, the medical dressing 1 further includes a second protective film 50 (see fig. 6) that releasably covers a surface of the top substrate 30 that is relatively distal from the middle layer 20. In this case, the second protective film 50 can maintain the surface of the top sheet 30 relatively distant from the intermediate layer 20 in a clean state before use, and when it is necessary to attach the medical dressing 1 to the wound surface 9, the second protective film 50 is peeled off from the surface, and the air permeability of the top sheet 30 is not affected.
In some examples, the protective film 40 and/or the second protective film 50 may be a release paper. This enables effective protection.
The medical dressing 1 according to the present disclosure can be used to protect a target surface, provide a moist tissue-contacting environment for the target surface, and be easily peeled off from the target surface.
A second aspect of the present disclosure relates to a method of manufacturing a medical dressing, by which the medical dressing can be used to protect a target surface, and which can absorb excess liquid from the target surface, provide a suitable moist environment for the target surface, and be easily peeled off from the target surface. In the present disclosure, the method of manufacturing the medical dressing may be simply referred to as "manufacturing method". The medical dressing prepared by the preparation method disclosed by the disclosure can be referred to as a dressing for short, and can also be referred to as a water-absorbing dressing, a wound dressing and the like.
When the medical dressing prepared by the preparation method disclosed by the disclosure is applied to a wound surface, a liquid layer formed by exudates secreted by the wound surface exists in at least part of the area between the wound surface and the medical dressing, so that a proper moist environment is provided for the wound surface, and in addition, a repair matrix carried on the medical dressing can be transferred to the wound surface, so that a good healing environment can be provided for the wound; when the wound surface is required to be stripped, the super-hydrophobic outer surface can reduce the adhesion with the granulation tissue of the wound, so that the wound surface is easy to strip from the wound surface, and secondary damage (namely secondary damage) to the wound is avoided.
Hereinafter, a method for producing a medical dressing according to the present disclosure will be described with reference to the drawings, taking a wound surface having an exuded liquid layer as an example of a target surface.
Fig. 7 is a schematic diagram illustrating a method of manufacturing a medical dressing 1 according to an example of the present disclosure.
In some examples, as described above, the medical dressing 1 may include a lower bottom layer 10, an intermediate layer 20, and an upper bottom layer 30 (see fig. 1) that are sequentially disposed in a stack. When the medical dressing 1 is applied to a target surface (a wound bed 9 having a exuded liquid layer 90), the lower substrate 10 may be in contact with the wound bed 9 and the intermediate layer 20 may be used to draw liquid from the wound bed 9 (see fig. 2).
In some examples, the medical dressing 1 may also include a water-soluble repair matrix. A repair matrix may be attached to the intermediate layer 20. In this case, when the medical dressing 1 is applied to the wound surface 9, the repair matrix can be dissolved in the exudate during the process of the middle layer 20 absorbing the exudate on the wound surface 9 and can be diffused to the wound surface 9 through the exudate for repair.
In some examples, the area of the wound surface 9 corresponding to the through hole 13 is referred to as a first area S1, and the area of the wound surface 9 corresponding to the unperforated area on the outer surface 12 of the lower base layer 10 is referred to as a second area S2. Referring to fig. 2, portions of a first region S1 and a second region S2 are schematically labeled.
In some examples, the lower base layer 10 may have an inner surface 11 facing the intermediate layer 20, and an outer surface 12 opposite the inner surface 11 (see fig. 2).
In some examples, the method of making the medical dressing 1 may include: preparing a lower base layer 10, and forming a plurality of through holes 13 penetrating through an inner surface 11 and an outer surface 12 in the lower base layer 10 (step S100); preparing an ultra-hydrophilic intermediate layer 20, wherein an adsorption structure is arranged in the intermediate layer 20 (step S200); attaching a water-soluble repair matrix to the adsorption structure of the intermediate layer 20 (step S300); preparing the upper and lower layers 30 having hydrophobicity (step S400); the upper back layer 30, the intermediate layer 20, and the lower back layer 10 are sequentially laminated to obtain the medical dressing 1 (step S500) (see fig. 7). It should be noted that, the order of step S100, step 200, and step S400 is not sequential, and should not be construed as being limiting. For example, step S100, step S200, and step S400 may be performed sequentially, simultaneously, or in a random order.
In some examples, in step S100, the intermediate layer 20 may absorb the liquid on the wound surface 9 through the through holes 13 by making a plurality of through holes 13 penetrating the inner surface 11 and the outer surface 12 on the lower base layer 10.
In some examples, in step S100, a plurality of micro-scale protrusions 141 may be arranged at intervals on the outer surface 12, and nanoparticles 142 are disposed on surfaces of the micro-scale protrusions 141. This enables the outer surface 12 to have superhydrophobicity. In the present disclosure, superhydrophobicity refers to the surface having a contact angle of a micro-drop of water greater than 150 ° and a rolling angle of less than 10 °. The micro-scale protrusions 141 and the nanoparticles 142 on the surfaces of the micro-scale protrusions 141 may be referred to as super-hydrophobic structures 14, and may also be referred to as micro-nano structures. That is, by disposing the superhydrophobic structure 14 on the outer surface 12, the contact angle of a micro water drop on the outer surface 12 can be made larger than 150 °, and the rolling angle is made lower than 10 °.
In some examples, when the medical dressing 1 prepared by the preparation method of the present disclosure is applied to a target surface having the liquid layer 90, liquid on a first area S1 of the target surface corresponding to the through-hole 13 is absorbed by the intermediate layer 20 via the through-hole 13 to keep the first area S1 and the through-hole 13 dry, and liquid on a second area S2 of the target surface corresponding to the superhydrophobic structure 14 is at least partially retained. In this case, when the target surface is the wound surface 9, the medical dressing 1 is applied to the wound surface 9, the first area S1 on the wound surface 9 can be in a dry environment through the adsorption of the intermediate layer 20 to the excess exudate of the wound, a part of the exudate can be maintained between the outer surface 12 and the second area S2 through the super-hydrophobic outer surface 12 of the lower bottom layer 10, and the second area S2 is in a moist tissue contact environment, so that not only can the adverse effect of dead cavities on wound healing be effectively avoided, but also a good healing environment can be provided for the wound surface 9; when the medical dressing 1 needs to be peeled off from the wound surface 9, because the second area S2 is in a humid environment, the superhydrophobic performance on the surface (namely the outer surface 12) of the lower bottom layer 10, which is in contact with the wound, can enable the lower bottom layer to show anti-adhesion performance to wound secretions, granulation tissues on the wound surface and the like, and can reduce adhesion between the outer surface 12 and the granulation tissues newly grown in the wound, so that the medical dressing is easy to peel off from the wound surface 9, thereby avoiding secondary damage to the wound, and because of the interval of the lower bottom layer 10, dressing fibers of the middle layer 20 are not easy to fall off to the wound surface 9, and foreign body reaction of the wound can be effectively reduced.
In some examples, in step S100, the through-hole 13 may have a cylindrical shape. That is, the through-hole 13 has a uniform hole diameter at the inner surface 11 and the outer surface 12. In this case, it can be facilitated that the intermediate layer 20 absorbs the liquid of the target surface through the through-holes 13.
In some examples, in step S100, the diameter of the through hole 13 may be 0.5mm to 3mm. In this case, it is possible to facilitate the intermediate layer 20 to absorb the liquid on the target surface from the through-holes 13 at an appropriate rate (see fig. 2, arrows schematically indicating the moving direction of the exudate during absorption of the exudate by the intermediate layer 20) to maintain the dryness of the through-holes 13 and the first region S1.
In some examples, in step S100, the pitch between two adjacent through holes 13 may be 1mm to 5mm. In some examples, the plurality of through holes 13 may be arranged in an array (see fig. 3). In this case, the unperforated regions (i.e., the regions provided with the superhydrophobic structures 14) on the outer surface 12 are also uniformly distributed, thereby enabling easy peeling.
In some examples, in step S100, the area of the open area on the outer surface 12 is no greater than 30% of the total area of the outer surface 12. That is, the plurality of through holes 13 occupy no more than 30% of the total area of the outer surface 12 on the outer surface 12. In this case, a large area of the wound surface 9 corresponding to the non-perforated area of the outer surface 12 can be maintained in a moist environment, which can facilitate healing of the wound surface 9 and also enable the medical dressing 1 to be easily peeled off from the wound surface 9.
In some examples, step S100 may further include disposing a superhydrophobic structure 14 on the outer surface 12 in an unperforated region. In this case, the plurality of micron-sized protrusions 141 and the nanoparticles 142 are disposed on the outer surface 12 of the lower base layer 10, so that the outer surface 12 has super-hydrophobicity, and when the medical dressing 1 is attached to the wound surface 9, a liquid layer 90 (see fig. 2) formed by exudate secreted by the wound surface 9 is formed between the outer surface 12 of the lower base layer 10 and the wound surface 9, so that the wound surface 9 is in a moist tissue contact environment, and the healing of the wound surface 9 is facilitated; when it is desired to peel the medical dressing 1 from the wound bed 9, adhesion between the outer surface 12 and the granulation tissue newly formed in the wound can be reduced due to the presence of the liquid layer 90, so that the medical dressing 1 can be easily peeled from the wound bed 9.
In some examples, in step S100, the micrometer-sized protrusions 141 may have a mastoid shape, a cone shape, or a column shape. In some examples, the height of the micro-scale protrusions 141 is 20 μm to 150 μm. In this case, it is possible to contribute to the improvement of the hydrophobic property of the outer surface 12, thereby contributing to the maintenance of a wet environment, and to the easy peeling.
In some examples, in step S100, the micro-scale protrusions 141 may be arranged in an array. In some examples, the pitch of the adjacent two micro-scale protrusions 141 may be 20 μm to 200 μm. In this case, the hydrophobic properties of the outer surface 12 are relatively uniform throughout, and the thickness of the liquid layer 90 formed by the liquid held between the second region S2 and the outer surface 12 can be substantially uniform, so that the healing rate of the second region S2 is substantially uniform, which is beneficial for the healing of the wound surface 9.
In some examples, in step S100, the nanoparticles 142 may be spherical, conical, cylindrical, or irregular solid. This can contribute to further improving the hydrophobic property of the outer surface 12, thereby facilitating maintenance of a wet environment and facilitating peeling.
In some examples, in step S100, the nanoparticle 142 may have a particle size ranging from 50nm to 1000nm. The particle size range refers to the diameter of the nanoparticles 142 when they are spherical, and refers to the equivalent diameter of the three-dimensional structure when they are not spherical.
In some examples, in step S100, the number of the nanoparticles 142 may be plural, and the particle diameters and shapes of the plural nanoparticles 142 may be the same or different (see fig. 5).
In some examples, in step S100, the superhydrophobic structure 14 may be integrally formed with the outer surface 12. In some examples, the material of the superhydrophobic structure 14 may be consistent with the material of the lower substrate layer 10. That is, the superhydrophobic structure 14 can be engraved on the outer surface 12 directly by means of, for example, laser machining. In this case, it can be convenient to prepare the lower base layer 10 having the superhydrophobic structure 14, and it can be advantageous to maintain the hydrophobicity of the outer surface 12.
In some examples, in step S100, the micro-scale protrusions 141 and/or nanoparticles 142 may be formed by laser etching on the outer surface 12 using a laser. Specifically, a femtosecond laser is used to perform laser etching on the outer surface 12 of the lower bottom layer 10 to form a dual-scale micro-nano structure, that is, a plurality of micron-scale protrusions 141 and a plurality of nano-particles 142 formed on the surfaces of the micron-scale protrusions 141 are formed on the outer surface 12, and after the laser etching, the outer surface 12 can be cleaned to remove surface impurity particles, so as to obtain the outer surface 12 provided with the superhydrophobic structure 14.
In some examples, in step S100, the parameters for performing laser etching on the outer surface 12 may be: the laser wavelength is 200nm to 400nm, the output power is 0.5W to 15W, the laser pulse width is 0.05ps to 10ps, the laser frequency is 10kHz to 1000kHz, and the beam scanning speed is 100mm/s to 5000mm/s. Considering that in the example that the lower bottom layer 10 is a PDMS film, the PDMS film is a colorless high-transmittance material, and has low laser absorption rate in the infrared band and the green band and high laser absorption rate in the ultraviolet band, the lower bottom layer 10 is processed by using laser with a wavelength of 200nm to 400 nm; in addition, the laser (which can be called as ultrafast laser or femtosecond laser) with the parameters has extremely high peak power, the heat effect generated in the processing process is small, and the damage to surrounding materials can be reduced, so that a micro-nano structure with higher precision can be prepared.
It should be noted that, limited by the existing processing precision, when the micro-nano structure is prepared, the prepared micro-scale protrusions 141 and/or nanoparticles 142 may not form a completely regular shape on a micro-scale layer, and the mastoid-like structure with a general profile having a certain height being relatively regular can play a role in water repellency as long as the mastoid-like structure is formed.
In some examples, in step S100, the superhydrophobic structure 14 may be disposed on the outer surface 12 such that the contact angle of the micro water drop on the outer surface 12 is greater than 150 ° and the rolling angle is less than 10 °. In this case, the superhydrophobic structure 14 disposed on the outer surface 12 can improve hydrophobicity, so that the outer surface 12 has superhydrophobic performance, thereby being beneficial to maintaining a moist environment between the outer surface 12 and the wound surface 9, and being easy to peel the medical dressing 1 off the wound surface 9.
In some examples, in step S100, the contact interface wetting state between the superhydrophobic structure 14 and the water-based micro-droplet is a stable Cassie-Baxter wetting state, the stability of which is represented by: 8 mu L of water-based micro-droplets are dropped on the surface of the super-hydrophobic structure 14 at the height of 0.3m in a free-falling mode, and the bouncing behavior is shown.
In some examples, in step S100, providing the superhydrophobic structure 14 on the inner wall of the through hole 13 may be further included. In this case, the liquid can be prevented from being caught on the inner wall of the through hole 13, which is advantageous for maintaining the dryness of the inside of the through hole 13.
In some examples, the lower base layer 10 may be prepared in a sheet shape in step S100.
In some examples, the thickness of the prepared bottom layer 10 may be 0.1mm to 2mm in step S100. It should be noted that, in the present disclosure, the thickness of the lower base layer 10 is the thickness of the whole including the micrometer-scale protrusions 141 and the nanoparticles 142. In this case, the lower base layer 10 is moderate in thickness and can maintain good air permeability, and can facilitate the middle layer 20 to absorb liquid from the target surface through the through-holes 13. In some examples, the thickness of the lower base layer 10 may be preferably 0.1mm to 1mm.
In some examples, in step S100, a hydrophobic material may be selected to prepare the lower base layer 10. This enables the lower floor layer 10 to have hydrophobicity. That is, the contact angle on the inner surface 11 of the lower base layer 10 and the through hole 13 may be greater than 90 °. In this case, it can be convenient to maintain a moist environment between the outer surface 12 and the wound bed 9.
In some examples, in step S100, the lower underlayer 10 may be prepared using silica gel. For example, the lower substrate 10 may be a silicon rubber film, which may also be referred to as a PDMS (polydimethylsiloxane) film. In this case, the upper and lower layers 30 are soft and have good biocompatibility and air permeability, and no irritation to human tissues, which can facilitate the healing of the wound surface 9.
In some examples, in step S200, a hydrophilic material may be selected to prepare the intermediate layer 20. In this case, the intermediate layer 20 has hydrophilicity. In some examples, the intermediate layer 20 may absorb liquid, and the liquid absorbed by the intermediate layer 20 may adhere to the intermediate layer 20, i.e., the liquid absorbed by the intermediate layer 20 may remain in the intermediate layer 20 without diffusing outward.
In some examples, in step S200, the intermediate layer 20 may have super-hydrophilicity. The contact angle of a water drop with the surface of the intermediate layer 20 is close to 0 deg., and the intermediate layer 20 is very easy to wet. In this case, the intermediate layer 20 can sufficiently absorb the excess exudate on the wound surface 9, and the exudate is easy to diffuse in the intermediate layer 20 after entering the intermediate layer 20, which is beneficial to improving the liquid absorption performance of the intermediate layer 20. In the present disclosure, superhydrophilic means that the contact angle of the surface with a drop of water is not more than 5 °. That is, the contact angle of the water droplet with the surface of the intermediate layer 20 having super hydrophilicity may be not more than 5 °. For example, the contact angle of a water droplet with the surface of the intermediate layer 20 having super hydrophilicity may be 5 °,4 °,3 °,2 °,1 °, 0.8 °, 0.6 °, 0.5 °, 0.3 °, 0.2 °, or 0.1 °.
In this case, the liquid on the first region S1 of the target surface corresponding to the through-hole 13 can be absorbed by the intermediate layer 20 via the through-hole 13, and the liquid in the through-hole 13 can also be absorbed by the intermediate layer 20, so that the first region S1 and the inside of the through-hole 13 can be kept dry, thereby making it possible to suppress adverse effects on wound healing such as dead space and the like, and provide a good healing environment for wound surface 9 healing. Wherein, as will be understood by those skilled in the art, keeping the first region S1 and the through hole 13 dry may refer to a relatively dry environment; specifically, the first region S1 and the inside of the through-hole 13 can be kept dry by the absorption of the exudate by the intermediate layer 20 in a normal case. It should be noted that, in some cases, due to the spacing of the lower bottom layer 10, the first region S1 is not in contact with the middle layer 20, and a part of the liquid on the surface of the first region S1 (for example, a part of the liquid on the first region S1 that is not in the through hole 13) may not be absorbed by the middle layer 20 in time, and the part of the liquid may still be absorbed by the middle layer 20 as it increases and flows to the vicinity of the through hole 13. This also falls within the scope of the present disclosure of "the first region S1 and the inside of the through-hole 13 are kept dry", that is, at least the dry atmosphere inside the through-hole 13 can be maintained by the adsorption of the intermediate layer 20.
That is to say, in the present disclosure, the adsorption through the intermediate layer 20 can not only maintain the wettability of the wound surface 9, but also effectively avoid the adverse effect of the dead space on the wound healing. In addition, in the present disclosure, the intermediate layer 20 can absorb excessive exudate, so that the wound surface 9 is wet but not soaked in liquid, and a good healing environment is provided for the wound surface 9.
In some examples, in step S200, the material of the intermediate layer 20 may include highly hydrophilic fibers. For example, in some examples, the material of the intermediate layer 20 may include sodium carboxymethyl cellulose. In this case, on the one hand, the intermediate layer 20 can be made super-hydrophilic, and on the other hand, the water retention effect of the intermediate layer 20 can be enhanced.
In some examples, the middle layer 20 may also include cotton wool in step S200. In some examples, the intermediate layer 20 may be a sponge sheet, a mesh nonwoven, or a medical cotton pad including cotton wool, or the like. In this case, the intermediate layer 20 has a high hydrophilicity and is soft in texture, can absorb excess exudate, and can provide a good healing environment for the wound bed 9.
In some examples, the intermediate layer 20 may be prepared in a sheet shape in step S200.
In some examples, the thickness of the prepared intermediate layer 20 may be 0.5mm to 5mm in step S200. In this case, the intermediate layer 20 has good air permeability and water absorption, can contribute to providing a good healing environment, and can give the medical dressing 1 as a whole good mechanical strength by the provision of the thickness of each functional layer. In some examples, the thickness of the intermediate layer 20 may be preferably 1mm to 1.5mm. In this case, the air permeability of the entire medical dressing 1 can be further optimized while having good water absorption properties.
In some examples, in step S200, the intermediate layer 20 may be configured such that the inside thereof may have different water absorbability.
In some examples, in step S200, the middle layer 20 may be configured such that the water absorption property is gradually increased from a lower surface relatively close to the lower substrate 10 to an upper surface relatively close to the upper substrate 30. For convenience of description, a portion of the middle layer 20 relatively close to the upper bottom layer 30 is referred to as an upper layer, and a portion relatively close to the bottom layer 10 is referred to as a lower layer (it does not mean that the middle layer 20 of the present disclosure includes only two layers with a well-defined interval). In the early stage of wound occurrence, the wound surface 9 secretes more exudate, in this case, when the medical dressing 1 is applied to the wound surface 9 in the early stage, the exudate of the wound surface 9 moves from the through hole 13 to be in contact with the lower layer of the intermediate layer 20 and is absorbed by the lower layer, compared with the intermediate layer 20 with uniform water absorption of the upper layer and the lower layer, because the water absorption of the upper layer of the intermediate layer 20 is greater than that of the lower layer in this example, most of the exudate in the lower layer tends to diffuse towards the upper layer, and only a small part of the exudate laterally diffuses in the lower layer, at this time, the unsaturated lower layer continues to rapidly absorb the exudate in the first region S1 and the through hole 13, thereby, the excess exudate on the wound surface 9 can be rapidly absorbed through the intermediate layer 20, and the relatively low-hydrophilic region of the lower layer helps to form an air cavity for adsorbing the liquid and the wound, so that good environmental healing can be provided for the wound surface 9 in the early stage.
In other examples, in step S200, the middle layer 20 may be configured such that the water absorption property is gradually increased from a position relatively close to the upper surface of the upper substrate 30 to a position relatively close to the lower surface of the lower substrate 10. In the middle and later stages of wound formation, the wound surface 9 secretes less exudate, and scabs may appear on a part of the wound surface 9, in this case, the water absorption of the lower layer of the intermediate layer 20 is stronger than that of the upper layer, when the medical dressing 1 is applied to the wound surface 9 in the middle and later stages, the exudate on the wound surface 9 is absorbed by the lower layer of the intermediate layer 20 through the through holes 13, most of the exudate in the lower layer tends to be spread laterally in the lower layer, most of the exudate is kept in the lower layer of the intermediate layer 20, the first area S1 on the wound surface 9 can be in a humid ambient air state, and therefore, a good healing environment can be provided for the wound surface 9 in the middle and later stages.
In some examples, in step S200, the interior of the intermediate layer 20 may have different water absorbability by configuring the intermediate layer 20 to be composed of different materials, or to be provided with different structures.
In some examples, in step S200, an adsorption structure may be prepared on the intermediate layer 20. This enables adsorption of the repair substrate.
In some examples, in step S200, the adsorption structure may be porous and the repair matrix may be attached to the adsorption structure. Wherein, the repair matrix can be a water-soluble material. In this case, in the process of adsorbing the exudate by the intermediate layer 20 through the through holes 13, the water-soluble repair matrix is dissolved in the exudate and is diffused to the wound surface 9 through the exudate, so that the healing of the wound surface 9 can be facilitated. That is, the repair matrix may be releasably attached to the absorbent structure. The repair matrix may be attached to the absorbent structure when it is not in contact with the liquid, and may dissolve in the liquid and undergo molecular diffusion movement within the liquid (i.e., be released by the absorbent structure) when it is in contact with the liquid.
In some examples, in step S200, the adsorption structure may include a mesh structure on the surface of the intermediate layer 20 and inside the intermediate layer 20. Thereby, adsorption of the repair substrate can be facilitated.
In some examples, in step S200, an adsorption structure may be disposed on a surface of the middle layer 20 relatively close to the lower base layer 10. For example, the adsorption structure may be a plurality of groove structures disposed on a surface of the middle layer 20 relatively close to the lower substrate 10. Thereby, the repair substrate can be accommodated and adsorbed by the groove structure.
In some examples, in step S300, the repair matrix may have water solubility. In this case, in the process of adsorbing the exudate by the intermediate layer 20 through the through holes 13, the water-soluble repair matrix is dissolved in the exudate and is diffused to the wound surface 9 through the exudate, so that the healing of the wound surface 9 can be facilitated.
In some examples, in step S300, the repair matrix may include mesenchymal stem cells and/or derivatives of mesenchymal stem cells. For example, in some examples, the repair matrix may include a supernatant of mesenchymal stem cells. The supernatant of the mesenchymal stem cells contains substances (e.g. active cytokines, RNA, polypeptides, and various bioactive substances, etc.) that can promote wound healing, in which case the healing matrix can facilitate wound healing when in contact with the wound bed 9.
In some examples, in step S300, mesenchymal stem cell-derived exosomes may be included in the supernatant of mesenchymal stem cells. Among them, exosomes are extracellular vesicles containing complex RNAs and proteins secreted by cells. Under the condition, the exosome derived from the mesenchymal stem cells can promote the healing of the wound surface 9 by using the paracrine effect, inhibit the inflammatory reaction of the wound surface 9, promote the angiogenesis, improve the extracellular matrix environment, mobilize the cells of the organism to migrate to the damaged part, and repair the wound surface 9.
In some examples, in step S300, one or more of vascular endothelial growth factor, epidermal growth factor, transforming growth factor-beta, liver growth factor, superoxide dismutase, interleukin-6, collagen, fibronectin, and platelet-derived factor may also be included in the supernatant of the mesenchymal stem cells. In this case, the healing of the wound can be advantageously promoted by the prosthetic matrix.
In some examples, in step S300, the supernatant of the mesenchymal stem cells may include one or more of exosomes of mesenchymal stem cells, vascular endothelial growth factor, epidermal growth factor, transforming growth factor-beta, liver growth factor, superoxide dismutase, interleukin-6, collagen, fibronectin, and platelet-derived factor. In this case, the repair ability of the repair matrix can be further improved, thereby promoting wound healing.
The present disclosure is not limited thereto, and the corresponding repair matrix may be selected according to the actual condition of the wound surface 9. For example, in some examples, the repair matrix may also include other components that aid in wound healing. For example, the repair matrix may also include a hemostatic powder, and the like.
In some examples, in step S300, the mesenchymal stem cell may be an umbilical cord mesenchymal stem cell, a bone marrow mesenchymal stem cell, or an adipose mesenchymal stem cell. In some examples, in step S300, the repair matrix may include umbilical cord mesenchymal stem cell exosomes, bone marrow mesenchymal stem cells, and/or adipose mesenchymal stem cell-derived exosomes.
In some examples, the repair matrix may include a plurality of mesenchymal stem cells and/or derivatives of mesenchymal stem cells. That is, in some examples, the repair matrix may include derivatives of one or more of umbilical cord mesenchymal stem cells, bone marrow mesenchymal stem cells, and adipose mesenchymal stem cells. Under the condition, various mesenchymal stem cells and derivatives thereof can be beneficial to wound healing, have rich sources, and can conveniently adjust the components of the repair matrix according to actual needs.
In some examples, in step S300, the repair matrix may be attached to the adsorption structure in the form of a lyophilized powder. In this case, compared to the stem cell supernatant in a liquid state, the concentration of the effective active cytokine per unit volume of the stem cell supernatant in a lyophilized powder form is higher, and the storage life of the bioactive substance is longer, and when the mesenchymal stem cell supernatant in a lyophilized powder form is loaded on the intermediate layer 20, the medical dressing 1 of the present disclosure can be conveniently stored and clinically applied.
In some examples, the repair matrix in powder form has a density of 0.5mg/cm on the surface of the middle layer 20 relatively close to the lower bottom layer 10 2 To 5mg/cm 2 . In this case, healing of the wound surface 9 can be facilitated.
In some examples, the repair matrix in powder form may be sprinkled evenly over the surface of the middle layer 20 adjacent to the lower bottom layer 10 and adsorbed by the middle layer 20. In other examples, the density of the repair matrix may be higher on a region of the surface of the intermediate layer 20 relatively close to the lower base layer 10 opposite to the through-holes 13 than other regions on the surface. Therefore, the repair matrix can be conveniently diffused to the wound surface 9 through the exudate in the process that the middle layer 20 absorbs the exudate from the through hole 13 so as to repair the wound surface 9.
In other examples, in step S300, the intermediate layer 20 may be immersed in the supernatant containing the exosomes of umbilical cord mesenchymal stem cells, and the intermediate layer 20 loaded with the supernatant may be freeze-dried, so that the repair matrix is releasably attached to the intermediate layer 20 and uniformly distributed in the intermediate layer 20.
Fig. 8 is a schematic diagram illustrating a method of making a repair matrix according to examples of the present disclosure.
In some examples, in step S300, taking a lyophilized powder of umbilical cord mesenchymal stem cell supernatant as a repair matrix as an example, the preparation method may include: taking Wharton' S jelly on the umbilical cord, and performing in vitro culture to obtain umbilical cord mesenchymal stem cells (step S31); subculture is performed (step S32); collecting cell supernatant and centrifuging after culturing for a predetermined time to obtain umbilical cord mesenchymal stem cell supernatant (step S33); a lyoprotectant is added to the supernatant of umbilical cord mesenchymal stem cells and freeze-dried to obtain a lyophilized powder of the repair matrix including the supernatant of umbilical cord mesenchymal stem cells (step S34) (see fig. 8). Wherein the Wharton's jelly is the gel filling between the amniotic membrane of umbilical cord and blood vessel. Therefore, the lyophilized powder of the repair matrix comprising the umbilical cord mesenchymal stem cell supernatant with good repair effect can be obtained. Of course, the embodiment is not limited thereto, and the lyophilized powder of the repair matrix including the umbilical cord mesenchymal stem cell supernatant may be obtained in other ways, which should not be construed as limiting.
In some examples, the umbilical cord mesenchymal stem cells obtained by the in vitro culture in step S31 may be recorded as P0 generation, and may be passaged 3-5 times in step S32, and the culture is continued by replacing the blank medium without serum after P3-P5 generation.
In some examples, the culturing for the predetermined time may range from 24h to 96h in step S33.
In some examples, in step S33, the supernatant of the umbilical cord mesenchymal stem cells may be further centrifuged at 800rpm/min to 2000rpm/min at 2 ℃ to 6 ℃ for 5min to 15min, and the supernatant may be taken and added with a lyoprotectant for freeze-drying. Under the condition, the method is favorable for further removing impurities and obtaining the umbilical cord mesenchymal stem cell supernatant with higher purity.
In some examples, after the supernatant of the umbilical cord mesenchymal stem cells is obtained in step S33, the supernatant may be examined for the content of key cytokines such as VEGF (vascular endothelial growth factor), EGF (epidermal growth factor), FGF, TGF- β (transforming growth factor- β), HGF (liver growth factor), SOD (superoxide dismutase), IL-6 (interleukin-6), collagen, FN (fibronectin), and platelet-derived factor (PDGF), RNA, polypeptide, and bioactive substances by enzyme-linked immunosorbent assay (ELISA or ELASA), and when the content is determined to be within a predetermined range, step S34 is performed. Among them, the cytokine is a small molecule protein synthesized/secreted by immune cells and partially non-immune cells by stimulation and having a wide range of biological activities, and can contribute to the repair of damaged tissues. Thereby, a lyophilized powder having desired repair properties can be conveniently obtained.
In some examples, in step S34, the lyoprotectant may include trehalose. In this case, the trehalose is used as the freeze-drying protective agent, so that the biological characteristics of the cytokines contained in the umbilical cord mesenchymal stem cell supernatant in the process of converting the umbilical cord mesenchymal stem cell supernatant into the freeze-dried powder can be effectively inhibited from changing, the activity of the cytokines can be maintained, the stability of the cytokines can be improved, the medical dressing 1 loaded with the repair matrix can be favorably stored and transported at normal temperature, and the storage life of the freeze-dried powder containing the cytokines can be prolonged.
In some examples, freeze-drying the supernatant in step S34 may include a pre-freezing phase, a sublimation phase, and a desorption phase. Specifically, the pre-freezing stage may reduce the temperature of the supernatant from room temperature to a first predetermined temperature and maintain the temperature for a first predetermined time; in the sublimation stage, the pre-frozen supernatant can be subjected to heating treatment under a preset pressure, so that the supernatant is heated to a second preset temperature; the desorption phase may be performed by raising the temperature again to raise the temperature of the supernatant to a third predetermined temperature for a third predetermined time. In this case, the whole supernatant can be sufficiently cooled to the first predetermined temperature by the pre-freezing stage, and the occurrence of an undesired characteristic change in the supernatant in the sublimation stage can be suppressed; the supernatant can be dehydrated and dried through a sublimation stage, and most of water in the supernatant is removed; the water in the supernatant can be further removed through the desorption stage, so that the freeze-dried powder of the umbilical cord mesenchymal stem cell supernatant rich in active cytokines and exosomes can be obtained.
The method for freeze-drying the supernatant is not limited to be applied to the umbilical cord mesenchymal stem cell supernatant, and can also be applied to freeze-drying other types of mesenchymal stem cell supernatants. In addition, the manner of freeze-drying the repair matrix to form the freeze-dried powder is not limited to the above method of freeze-drying the supernatant, and other methods may be used to prepare the repair matrix in the form of the freeze-dried powder.
In some examples, the first predetermined temperature may be-40 ℃. In this case, the glass transition of the active ingredient in the supernatant can be facilitated. In some examples, the first predetermined time may be 40min to 70min. For example, the first predetermined time may be 40min, 45min, 50min, 55min, 60min, 65min, or 70min.
In some examples, the sublimation stage and desorption stage may be performed within a vacuum oven.
In some examples, the predetermined pressure may be 0.13mbar to 0.3mbar in the sublimation stage. In this case, sublimation of moisture in the supernatant can be facilitated.
In some examples, the second predetermined temperature may be 4 ℃. Thus, the supernatant lyophilized powder in the low temperature state can be obtained. In some examples, the temperature of the supernatant may be raised from a first predetermined temperature to a second predetermined temperature using a two-time sublimation process. For example, in some examples, the first predetermined temperature is-40 ℃ and the second predetermined temperature is 4 ℃, and the temperature of the supernatant may be increased to-20 ℃ in the first temperature increase and then increased from-20 ℃ to 4 ℃ in the second temperature increase. Under the condition, the phenomenon of internal and external layering caused by over-fast temperature rise/over-large temperature difference can be inhibited, so that the supernatant freeze-dried powder which is uniformly dried is favorably formed.
In some examples, the duration of the first warming may be around 60 min. The duration of the second heating can be controlled to be about 90 min. In this case, it can be advantageous for the supernatant as a whole to be sufficiently shifted to the corresponding target temperature.
In some examples, the predetermined pressure may be 0.18 to 0.28mbar in the desorption phase. In this case, the water in the supernatant can be further removed.
In some examples, the third predetermined temperature may be-30 ℃. In some examples, the third predetermined time may be 150min to 180min. For example, the third predetermined time may be 150min, 155min, 160min, 165min, 170min, 175min, or 180min.
In some examples, the duration of the process of transitioning the supernatant from the second predetermined temperature to the third predetermined temperature in the desorption phase may be less than 30min. That is, the supernatant may be transitioned from the second predetermined temperature to the third predetermined temperature within 30min. In this case, it is advantageous to maintain the activity of a substance such as a cytokine in the supernatant.
In some examples, the medical dressing 1 may be applied to the wound bed 9 prior to applying the medical dressing 1 to the wound bed 9, and then the medical dressing 1 may be applied to the wound bed 9. The components of the medicine can be the same as those of the repairing matrix, and can also be other components capable of promoting wound healing. In this case, the repair matrix can be used in combination with a drug to further improve the ability of the repair to the wound, thereby promoting wound healing. For example, in some examples, the composition of the drug may also include exosomes of umbilical cord mesenchymal stem cells, and the drug may also be present in the form of a lyophilized powder, in which case the drug may be uniformly sprinkled on the wound surface 9 before the medical dressing 1 is applied to the wound surface 9. Under the condition, the exosome of the umbilical cord mesenchymal stem cells can exert the biological effect of the umbilical cord mesenchymal stem cells, and the wound surface 9 is promoted to heal.
In some examples, in step S400, a hydrophobic material may be selected to prepare the upper layer 30. This can make the top sheet 30 hydrophobic. In this case, contaminants in the external environment (particularly, liquid that may carry bacteria/germs) can be effectively prevented from entering the dressing 1 through the upper bottom layer 30, and a barrier effect is achieved, so that the infection risk of the wound surface 9 is reduced.
In some examples, the upper and lower layers 30 may be prepared in a sheet shape in step S400.
In some examples, the thickness of the prepared upper bottom layer 30 may be 0.2mm to 1mm in step S400. In this case, the upper and lower layers 30 have good air permeability and strong mechanical strength, and can effectively play a barrier role and provide a good healing environment for the wound surface 9. In some examples, the upper bottom layer 30 may preferably have a thickness of 0.2mm to 0.5mm. In this case, the breathability of the upper back layer 30 can be further improved while functioning as a barrier.
In some examples, the upper and lower layers 30 may be prepared using silica gel in step S400. For example, the upper substrate layer 30 may be a silicone rubber film, which may also be referred to as a PDMS (polydimethylsiloxane) film. In this case, the upper and lower layers 30 are soft and have good air permeability, and can provide a good healing environment for the wound surface 9.
In some examples, in step S400, the superhydrophobic structure 14 may be disposed on a surface of the upper bottom layer 30 facing the middle layer 20, and a surface opposite to the surface, respectively. In this case, the hydrophobicity of the two surfaces of the upper bottom layer 30 can be enhanced, so that the outward evaporation of the exudate in the middle layer 20 can be inhibited, and a proper moist environment can be provided for the wound surface 9; in addition, the pollution resistance of the upper bottom layer 30 can be further enhanced, and the infection risk of the wound surface 9 is reduced.
In some examples, in step S500, adjacent two of the upper bottom layer 30, the middle layer 20, and the lower bottom layer 10 may be bonded to each other by an adhesive, and no adhesive is provided in a region of the middle layer 20 corresponding to the through-hole 13. In this case, the layers can be tightly bonded to each other, and the intermediate layer 20 is facilitated to absorb liquid of the target surface through the through-holes 13.
In some examples, in step S500, an adhesive may be applied to the outer peripheral region between the middle layer 20 and the lower base layer 10 to bond the middle layer 20 and the lower base layer 10 to each other.
In some examples, the lower base layer 10, the middle layer 20, and the upper base layer 30 may be prepared in a sheet shape in the above steps. In some examples, in step S500, the lower bottom layer 10, the intermediate layer 20, and the upper bottom layer 30 are sequentially stacked to obtain the medical dressing 1 in a sheet shape. Thereby, covering of the target surface can be facilitated.
In other examples, the lower substrate layer 10, the intermediate layer 20, and the upper substrate layer 30 may be prepared in the above-described steps as an elongated sheet shape, and the lower substrate layer 10, the intermediate layer 20, and the upper substrate layer 30 may be sequentially laminated in step S500 to obtain the medical dressing 1 in an elongated sheet shape (i.e., in a long roll shape). In such a case, the medical dressing 1 may be cut to a desired size (e.g., a shape that can cover the wound bed 9) for use.
In some examples, the medical dressing 1 may have a length of 20mm to 120mm and a width of 20mm to 120mm. In this case, it can be fitted to the small wound surface 9 and is portable. The present disclosure is not limited thereto, and the size of the medical dressing 1 may also be adjusted according to actual needs. For example, when the area of the target surface is large, it may be protected with the medical dressing 1 capable of covering the size of the target surface.
In some examples, the medical dressing 1 may be attached to the wound bed 9 by medical tape. In step S400, the two ends of the upper bottom layer 30 may be extended outward, and the inner walls of the two ends of the upper bottom layer 30 extended outward are provided with an adhesive, so as to form a band-aid, which can facilitate the medical dressing 1 to be attached to the wound surface 9.
In some examples, the manufacturing method of the present disclosure may produce a medical dressing 1 having a lifetime of 0.5 to 3 days. In some examples, the medical dressing 1 preferably has a lifetime of 12 to 36 hours. The term of use refers to the length of time that the medical dressing 1 is applied to the target surface. In this case, it is possible to contribute to maintaining good air permeability and provide a suitable healing environment for the wound surface 9.
In some examples, a protective film 40 (see fig. 6) that releasably covers the outer surface 12 may also be disposed on the outer surface 12 of the lower chassis layer 10. In this case, the outer surface 12 can be maintained in a clean state before use by providing the protective film 40, and when it is necessary to attach the medical dressing 1 to the wound surface 9, the protective film 40 may be peeled off from the outer surface 12.
In some examples, the shape of the protective film 40 may conform to the shape of the lower base layer 10. For example, in the embodiment where the lower base layer 10 is sheet-shaped, the protective film 40 may also be sheet-shaped, and the area of the protective film 40 in sheet shape is not smaller than the area of the outer surface 12 of the lower base layer 10.
In some examples, a second protective film 50 (see fig. 6) releasably covering a surface of the upper substrate 30 relatively far from the middle layer 20 may also be provided on the surface. In this case, the second protective film 50 can maintain the surface of the top sheet 30 relatively distant from the intermediate layer 20 in a clean state before use, and when the medical dressing 1 needs to be applied to the wound surface 9, the second protective film 50 is peeled off from the surface, and the air permeability of the top sheet 30 is not affected.
In some examples, the protective film 40 and/or the second protective film 50 may be a release paper. This enables effective protection.
According to the production method relating to the second aspect of the present disclosure, the medical dressing 1 that can be used for protecting a target surface, can provide a moist tissue contact environment for the target surface, and can be easily peeled off from the target surface can be produced.
While the present disclosure has been described in detail above with reference to the drawings and the embodiments, it should be understood that the above description does not limit the present disclosure in any way. Variations and changes may be made as necessary by those skilled in the art without departing from the true spirit and scope of the disclosure, which fall within the scope of the disclosure.

Claims (10)

1. A medical dressing having a repair matrix, characterized by:
comprises a middle layer, a water-soluble repair substrate arranged on the middle layer, and an upper bottom layer and a lower bottom layer which are respectively arranged on two opposite sides of the middle layer,
the intermediate layer has super-hydrophilicity and has different water absorbability in the longitudinal direction inside, the intermediate layer has an adsorption structure in a porous shape to which the repair substrate is attached,
the upper bottom layer has a hydrophobic property,
the lower base layer has an inner surface facing the intermediate layer, an outer surface opposite to the inner surface, a plurality of through holes penetrating the inner surface and the outer surface, and a superhydrophobic structure provided on the outer surface, when the medical dressing is applied to a target surface having a liquid layer, liquid on a first region of the target surface corresponding to the through holes is absorbed by the intermediate layer via the through holes to keep the first region and the through holes dry, liquid on a second region of the target surface corresponding to the superhydrophobic structure is at least partially retained, and the repair matrix is dissolved in the liquid and diffused to the target surface by the liquid during absorption of the liquid on the first region by the intermediate layer via the through holes.
2. The medical dressing of claim 1, wherein:
the middle layer has a lower surface facing the lower base layer and an upper surface facing the upper base layer, and the water absorption of the middle layer gradually increases or gradually decreases from the lower surface to the upper surface.
3. The medical dressing of claim 1, wherein:
the repair matrix comprises a supernatant of mesenchymal stem cells.
4. A medical dressing as claimed in claim 1 or claim 3, wherein:
the repair matrix is attached to the adsorption structure in the form of a lyophilized powder.
5. The medical dressing of claim 1, wherein:
the area of the open area on the outer surface is no greater than 30% of the total area of the outer surface.
6. The medical dressing of claim 1, wherein:
the superhydrophobic structure includes a plurality of micro-scale protrusions spaced on the outer surface, and nanoparticles disposed on surfaces of the micro-scale protrusions.
7. The medical dressing of claim 6, wherein:
the height of the micron-sized protrusions is 20-150 microns, the micron-sized protrusions are arranged in an array mode, and the distance between every two adjacent micron-sized protrusions is 20-200 microns.
8. The medical dressing of claim 6, wherein:
the nanoparticles are spherical, conical, or columnar, and the particle size of the nanoparticles is 50nm to 1000nm.
9. The medical dressing of claim 1, wherein:
the inner wall of the through hole is provided with the super-hydrophobic structure.
10. The medical dressing of claim 1, wherein:
the through-hole is cylindric to the diameter of through-hole is 0.5mm to 3mm, and the interval of two adjacent through-holes is 1mm to 5mm.
CN202211287212.3A 2022-05-26 2022-10-20 Medical dressing with repair matrix Pending CN115645150A (en)

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CN113413267A (en) * 2021-06-22 2021-09-21 元睦生物科技(上海)有限公司 High-absorptivity wound dressing

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CN104287890A (en) * 2010-06-01 2015-01-21 株式会社瑞光 Surface sheet for wound dressing and wound dressing
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CN117137726B (en) * 2023-10-27 2023-12-22 江苏益仁堂生物科技有限公司 Collagen repair patch and preparation method thereof

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